[A multi-center study on the long-term mortality and related risk factors in patients with chronic heart failure receiving resynchronization therapy].

Objective: To analyze long-term mortality and patients characteristics of cardiac resynchronization therapy (CRT) for patients with chronic heart failure. Methods: In-patients with chronic heart failure who received CRT in the three medical centers(Bethune International Peace Hospital, General Hospital of Shenyang Military Command of Chinese People's Liberation Army, and 251 Hospital of People's Liberation Army)from March 2001 to June 2013 were included.Mortality and related causes, echocardiographic parameters were analyzed. Results: A total of 200 patients were treated with CRT therapy (154 males, mean age (60.57±11.75) years), 59 cases suffered from ischemic cardiomyopathy (ICM), patients were followed up from 0.5 to 12 years.The all-cause mortality rate was 25.50% (51/200), 20 out of 59 (33.90%) ICM patients died, as compared with 31 deaths out of 141 (21.98%) in non-ischemic cardiomyopath (NICM) patients.Thirty-six patients died due to cardiac death (70.59%), in which sudden death occurred in 21 patients (41.18%). Non-cardiac death occurred in 13 patients (25.49%), two patients died due to unknown reasons (3.92%). Incidence of cardiac death was significantly higher than non-cardiac death (P<0.01). The main cause for cardiac death was NICM (28/36, 77.78%), while the main cause of non-cardiac death was ICM (11/13, 84.62%, P<0.01). Patients died due to cardiac death were younger (P<0.01) and had larger left atrial end-diastolic diameter (LAEDD) and left ventricular end-diastolic diameter (LVEDD) (P<0.01), lower left ventricular ejection fraction (LVEF)(P<0.05), higher pulmonary artery pressure(P<0.05) compared to patients with non-cardiac death.One hundred and fifty-two cases received CRT-P and 48 cases received CRT-D, there were no significant differences in gender, the course of heart failure, serum creatinine levels, pre-operative and post-operative QRS duration and so on between the CRT-P and CRT-D groups(all P>0.05). Eleven out of the 48 cases with CRT-D died during the following-up (21.57%) , while 40 out of 152 cases with CRT-P died (78.43%) during the following-up(χ2=3.13, P<0.01). The proportional mortality rate in cause of death in patients with CRT-D was non-cardiac while in those with CRT-P was cardiac (χ2=2.66, P<0.01), sudden death rate was also significantly higher in CRT-P group than in CRT-D group (χ2=2.16, P<0.01). By using single- and multiple-factor Cox regression analysis, age, disease course, pre-operation QRS duration and NYHA classification were predictors of cardiac death(all P<0.05). Conclusions: The all-cause mortality of CRT is 25.50% in this patient cohort, mortality rate was higher in ICM patients than in NICM patients.Sudden cardiac death rate was the highest mortality reason.The mortality rate of patients with CRT-P was significantly higher than in patients with CRT-D.In comparison with patients of non-cardiac death, patients of cardiac death had larger left atrium and left ventricle and worse heart function before CRT implantation.

[Salubrinal improves cardiac function in rats with heart failure post myocardial infarction through reducing endoplasmic reticulum stress-associated apoptosis].

OBJECTIVE: Endoplasmic reticulum (ER) stress plays an important role in ischemia-mediated cell death. The aim of the current study is to investigate the effects of salubrinal (Sal), a selective eIF2a dephosphorylation inhibitor, on heart failure rats and related mechanisms. METHODS: Heart failure was induced by coronary artery ligation (MI) in adult male Sprague-Dawley rats. To ensure comparable MI sizes post coronary artery ligation on various groups, echocardiography examination was performed before and 30 minutes after ligation in MI groups. Then rats were randomly assigned to 4 groups: Sham group (n=12), MI group (n=10), MI plus vehicle injections group (DMSO group, n=12) and MI plus Sal injection group (Sal group, n=12). Sal (1 mg/kg) or DMSO was injected via the tail vein daily for the first 3 days (starting at 30 minutes after ligation of the left coronary artery), followed by subcutaneous injections twice per week for 8 weeks. Cardiac function was assessed by echocardiography and cell apoptosis assessed by flow cytometric analysis after 8 weeks. Protein and mRNA levels of ER stress markers were evaluated by immunohistochemistry and real time RT-PCR respectively. RESULTS: Eight weeks later, LVEF was significantly higher, while LVESD and LVEDD values were significantly lower in Sal group compared to MI and DMSO groups (all P<0.05); LV/BW ratio was significantly higher in MI group than in Sham group ((2.30±0.40) mg/g vs.(1.78±0.31) mg/g, P<0.05), which was significantly reduced in Sal group ((1.88±0.25) mg/g), but not in DMSO group((2.25±0.36) mg/g, P<0.05 vs. MI). In addition, flow cytometric analysis showed that Sal treatment significantly reduced apoptosis but not necrosis in post MI. Immunohistochemistry and real time PCR analysis showed that the myocardial protein and mRNA expression of ER stress markers were significantly lower in Sal group than in MI group, myocardial caspase-12 expression was significantly upregulated in MI group and significantly reduced by Sal treatment. CONCLUSIONS: Our results suggest that reduction of ER stress and myocardial apoptosis through inhibition of eIF2α dephosphorylation may serve as the potential mechanisms for the improved cardiac function and attenuated cardiac remodeling post Sal treatment in this heart failure rat model.